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Target Concepts:
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Query: UNIPROT:P21554 (
cannabinoid receptor
)
3,582
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Type 1 cannabinoid receptors (CB1Rs) are widely expressed in the vertebrate retina, but the role of endocannabinoids in vision is not fully understood. Here, we identified a novel mechanism underlying a
CB1R
-mediated increase in retinal ganglion cell (RGC) intrinsic excitability acting through AMPK-dependent inhibition of
NKCC1
activity. Clomeleon imaging and patch clamp recordings revealed that inhibition of
NKCC1
downstream of
CB1R
activation reduces intracellular Cl(-) levels in RGCs, hyperpolarizing the resting membrane potential. We confirmed that such hyperpolarization enhances RGC action potential firing in response to subsequent depolarization, consistent with the increased intrinsic excitability of RGCs observed with
CB1R
activation. Using a dot avoidance assay in freely swimming Xenopus tadpoles, we demonstrate that
CB1R
activation markedly improves visual contrast sensitivity under low-light conditions. These results highlight a role for endocannabinoids in vision and present a novel mechanism for cannabinoid modulation of neuronal activity through Cl(-) regulation.
...
PMID:Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells. 2750 34